The objective of this research is to study the thymic factor induced differentiation of pro-thymocytes into thymoctyes. We have observed that the expression of differentiation antigens (Thy-1) on BSA gradient-purified marrow cells occurs within one hour of treatment. This expression may be initiated with a cell surface modifying enzyme--neuraminidase. We plan to study the mechanism of expression of the differentiation antigens using cell surface probes and membrane labeling techniques. The fluidity and organization of the differentiating membrane will be studied by fluorescent membrane probes. The immunochemistry of Thy-1 and GM1 ganglioside will be explored by isolation and biochemical characterization of the antigens and a thymocyte plaque assay will be used to study the immunogenicity of purified gangliosides and glycoproteins. This will enable us to study their expression as cell surface antigens on thymocytes and T cells. The biochemistry of shedding of membrane complexes containing differentiation antigens will be examined and purified membrane complexes will be tested for their functional role in modulation of the B cell response. These experiments will lead us to understand the initial changes in membrane expression which accompany the early differentiation of T cells. The knowledge acquired will be applied to the rational development of agents capable of controlling thymocyte differentiation in lymphoproliferative disorders as in leukemias, in the immune response to cancer, transplant rejections, and in autoimmune diseases.